The Molecular Genetics of High Myopia

描述(由申请人提供)：该申请是一项综合性研究的一部分，目的是从分子上确定与严重近视或近视有关的人类基因。当聚焦的图像落在眼睛的视网膜光感受器层之前时，就会发生近视。近视是人类最常见的眼病，严重者可能会导致早发性白内障、青光眼、视网膜脱离和黄斑变性等致盲疾病。近视是一个巨大的公共健康问题，在美国被列为第四大致盲原因。虽然以近视为临床特征的遗传综合征是一种临床特征，但近视确实是以遗传性的方式发生的，作为一种孤立的情况。有大量证据表明，遗传因素在非综合征性高度近视的发生发展中起着重要作用。本实验室已经定位了3个常染色体显性高度近视基因座(MYP2-染色体18p11.31，MYP3-染色体12q23.1-q24，以及染色体17q21-q22上的一个基因座)，并提炼了X连锁高度近视基因座(Xq28上的MYP1)。这项建议的具体目的是：1)识别和招募高度近视家庭，以定位和完善现有的近视基因座；以及2)使用位置候选基因筛选方法识别MYP2基因。MYP2基因的鉴定将有助于确定经典高度近视的遗传基础，并可能为深入了解近视的分子基础提供帮助。近视基因突变的检测将有助于我们了解眼睛的生长发育，并为研究其他屈光障碍的遗传病因提供一个框架。识别与近视易感性有关的基因将为近视的发生提供一个基本的分子理解，并可能导致定向的生理学(即药物、基因治疗)干预。这一努力将有助于我们的长期目标，即为这种潜在的致盲眼病的严重形式制定诊断和治疗策略，目前这种疾病还没有有效的治疗方法。

DESCRIPTION (provided by applicant): The proposed application is part of a comprehensive research effort to molecularly define human genes that are implicated in severe nearsightedness, or myopia. Myopia occurs when the focused image falls anterior to the retinal photoreceptor layer of the eye. Myopia is the most common human eye disease, and severe cases may lead to blinding disorders such as premature cataracts, glaucoma, retinal detachment, and macular degeneration. Myopia is an enormous public health problem, and has been cited as the 4th leading cause of blindness in the United States. While there are genetic syndromes with myopia as a clinical feature, myopia does occur in an inherited fashion as an isolated condition. There is substantial evidence that genetic factors play a significant role in the development of non-syndromic high myopia. Our laboratory has mapped three autosomal dominant high myopia loci (MYP2- chromosome 18p11.31, MYP3 - chromosome 12q23.1-q24, and a locus at chromosome 17q21-q22), and refined the X-linked high myopia locus (MYP1 at chromosome Xq28). The Specific Aims of this proposal are to: 1) identify and recruit families with high myopia to map and refine existing myopia loci; and 2) identify the MYP2 gene using a positional candidate gene screening approach. Identification of the MYP2 gene will help define the genetic basis of classic high myopia, and may provide insight into the molecular basis of myopia. The determination of myopia gene mutations will contribute to our understanding of eye growth and development, as well as provide a framework for examining the genetic etiology of other refractive disorders. Identifying the implicated genes for myopia susceptibility will provide a fundamental molecular understanding of how myopia occurs, and may lead to directed physiologic (i.e. pharmacologic, gene therapy) interventions. This effort will contribute to our long-term goal to devise diagnostic and therapeutic strategies for the severe forms of this potentially blinding eye disease, which presently has no effective treatment.